Synthetic chord

ABSTRACT

Synthetic chord devices and methods for using the same for connecting tissues are provided. Aspects of the synthetic chord device include a flexible cord having an attachment element at both a first and a second end, wherein each attachment element includes a piercing member coupled to a securing member that attaches the flexible cord to a first tissue. At least a portion of the flexible cord can be configured to be secured to a second tissue. Aspects of the invention also include sets of the synthetic chord device with pre-measured flexible cords. The devices and methods of the invention find use in a variety of applications, such as in applications in which it is desired to repair a heart valve.

INTRODUCTION

The mitral valve is composed of two leaflets attached to the mitralvalve annulus, which are supported at the free edge by chordae tendinae(chords) attached to the inside wall of the left ventricle and to thepapillary muscles. However, sometimes one or both of the valve leafletsbecome loose, due to loosening or failure of one or more of thesechords. The valve then prolapses, and the seal that it normally providesbetween the left atrium and left ventricle becomes compromised, causingthe blood to flow back into the left atrium during systole.

A variety of methods have been described for placement of artificialchordae tendineae to correct mitral valve leaflet prolapse and treatdiseased mitral valve chordae tendineae. However, there are manytechnical challenges in this surgical procedure, especially whenperformed with minimally invasive techniques. The most common method ofrepairing the valves is to create synthetic chordae tendineae frompolytetrafluoroethylene (PFTE), which are sutured into place between thepapillary muscle of the heart wall and the mitral valve leaflets.Cardiac surgeons usually are required to perform the time-consumingprocess of measuring and cutting the necessary length of syntheticchordae tendineae material during the surgical procedure after they havemeasured the dimensions of the patient's heart valves. In addition,anchoring the synthetic chordae tendineae in the papillary muscle andsecuring the sutures through the leaflets is often technically difficultin minimally invasive procedures, because of limitations in using2-dimensional video for viewing the surgical field, limited exposure ofthe surgical field, and limited degrees of freedom using standardthoracoscopic instrumentation.

Therefore, there is considerable interest in the development of newtechniques for use in both open and minimally invasive procedures thataddress the problems of accurately and efficiently securing the valveleaflets during cardiac surgery.

SUMMARY

Synthetic chord devices and methods for using the same for connectingtissues are provided. Aspects of the synthetic chord devices of theinvention include a flexible cord having attachment elements at both afirst and second end, wherein each attachment element includes apiercing member coupled to a securing member, where the securing memberattaches the flexible cord to a first tissue. At least a portion of theflexible cord is configured to be secured to a second tissue. Aspects ofthe invention also include sets of the synthetic chord devices, e.g., ofdifferent sizes. The devices and methods of the invention find use in avariety of applications, such as in applications in which it is desiredto repair a heart valve.

BRIEF DESCRIPTION OF THE FIGURES

FIGS. 1A and B provide a view of the device in accordance with anembodiment of the invention.

FIG. 2 provides a schematic view of the normal left side of the heart.

FIG. 3 provides a schematic view of the left side of the heartdemonstrating a ruptured chorda tendinea of the mitral valve.

FIGS. 4A and B provide a schematic view of the left side of the heartafter repair of the ruptured chorda tendinea of the mitral valve withembodiments of the synthetic chord device of the subject invention.

FIGS. 5A and 5B provide another view of the device in accordance with anembodiment of the invention.

FIG. 6 provides a schematic view of the heart after repair of both theruptured chordae tendineae of the mitral valve and tricuspid valves withembodiments of the synthetic chord device of the subject invention.

DETAILED DESCRIPTION

Synthetic chord devices and methods for using the same for connectingtissues are provided. Aspects of the synthetic chord devices include aflexible cord having an attachment element at both a first and a secondend, wherein each attachment element includes a piercing member coupledto a securing member that attaches the flexible cord to a first tissue.At least a portion of the flexible cord is configured to be secured to asecond tissue. Aspects of the invention also include sets of thesynthetic chord devices, e.g., of different sizes. The devices andmethods of the invention find use in a variety of applications, such asin applications in which it is desired to repair a heart valve.

Before the present invention is described in greater detail, it is to beunderstood that this invention is not limited to particular embodimentsdescribed, as such may, of course, vary. It is also to be understoodthat the terminology used herein is for the purpose of describingparticular embodiments only, and is not intended to be limiting, sincethe scope of the present invention will be limited only by the appendedclaims.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range, is encompassed within the invention. The upper and lowerlimits of these smaller ranges may independently be included in thesmaller ranges and are also encompassed within the invention, subject toany specifically excluded limit in the stated range. Where the statedrange includes one or both of the limits, ranges excluding either orboth of those included limits are also included in the invention.

Certain ranges are presented herein with numerical values being precededby the term “about.” The term “about” is used herein to provide literalsupport for the exact number that it precedes, as well as a number thatis near to or approximately the number that the term precedes. Indetermining whether a number is near to or approximately a specificallyrecited number, the near or approximating unrecited number may be anumber which, in the context in which it is presented, provides thesubstantial equivalent of the specifically recited number.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although any methods andmaterials similar or equivalent to those described herein can also beused in the practice or testing of the present invention, representativeillustrative methods and materials are now described.

All publications and patents cited in this specification are hereinincorporated by reference as if each individual publication or patentwere specifically and individually indicated to be incorporated byreference and are incorporated herein by reference to disclose anddescribe the methods and/or materials in connection with which thepublications are cited. The citation of any publication is for itsdisclosure prior to the filing date and should not be construed as anadmission that the present invention is not entitled to antedate suchpublication by virtue of prior invention. Further, the dates ofpublication provided may be different from the actual publication dateswhich may need to be independently confirmed.

It is noted that, as used herein and in the appended claims, thesingular forms “a”, “an”, and “the” include plural referents unless thecontext clearly dictates otherwise. It is further noted that the claimsmay be drafted to exclude any optional element. As such, this statementis intended to serve as antecedent basis for use of such exclusiveterminology as “solely,” “only” and the like in connection with therecitation of claim elements, or use of a “negative” limitation.

As will be apparent to those of skill in the art upon reading thisdisclosure, each of the individual embodiments described and illustratedherein has discrete components and features which may be readilyseparated from or combined with the features of any of the other severalembodiments without departing from the scope or spirit of the presentinvention. Any recited method can be carried out in the order of eventsrecited or in any other order which is logically possible.

Devices

Synthetic chord devices according to certain embodiments of theinvention are devices that are configured to connect or align tissues,or connect tissue and a prosthesis, or a combination thereof. Thesubject devices and methods can be used in endovascular, minimallyinvasive surgical, open surgical, or other interventional procedures. Assuch, devices of the invention can be configured to secure a valveleaflet, such as a mitral valve leaflet or tricuspid valve leaflet, to apapillary muscle.

Embodiments of the synthetic chord device include a flexible cord havingan attachment element at both a first and a second end, wherein eachattachment element includes a piercing member coupled to a securingmember that attaches the flexible cord to a first tissue. At least aportion of the flexible cord can be configured to be secured to a secondtissue.

A synthetic chord device of the subject invention is a synthetic, orartificial, flexible cord which has attachment elements at both ends ofthe cord, for attaching the cord to a tissue. In some embodiments, theflexible cord is configured to be attached to a prosthesis, or to adevice that substitutes for or supplements a missing or defective partof the body, e.g., a synthetic cardiac valve, or a porcine valve. Insome embodiments, a synthetic chord device is configured to be used as asynthetic chorda tendinea for use in repair of a cardiac valve, e.g.,the mitral valve.

The flexible cord element of the subject invention is a flexibleelongated structure having a first end and a second end, constructed ofa material suitable for use in the body that can be used in the methodsof the subject invention, e.g., attaching a valve leaflet to theunderlying cardiac tissue. The flexible cord element has a lengthsuitable for extending from a first tissue to a second tissue and backto a first tissue, such that the flexible cord provides two segments,each segment secured to both the first and the second tissue. Forexample, in certain embodiments, each segment of the flexible cord wouldbe equal to half of the total length of the flexible cord. In someembodiments, the flexible cord element has a length suitable forextending from a first tissue (e.g., a mitral valve leaflet) to where itis secured to a second tissue (e.g., a papillary muscle) and back to thefirst tissue. In this embodiment the length of the flexible cord mayrange from 8 mm to 60 mm, such as from 16 mm to 48 mm, or 20 mm to 32mm. In some embodiments, the first or second end of the flexible cordcan be secured to a prosthesis, or other device that substitutes for orsupplements a missing or defective part of the body, e.g., a syntheticcardiac valve, or a porcine valve.

The flexible cord can be made of a variety of biocompatible polymericmaterials or metallic materials that combine flexibility, high strength,and high fatigue resistance. For example, the flexible cord can beformed using materials including, but not limited to:polytetrafluoroethene or polytetrafluoroethylene (PFTE), includingexpanded polytetrafluoroethylene (e-PFTE), polyester (Dacron™), nylon,polypropylene, polyethylene, high-density polyethylene (HDPE),polyurethane, stainless steel, titanium, a nickel-titanium alloy, anickel-cobalt alloy, another cobalt alloy, tantalum, and combinations ormixtures thereof. In some embodiments, an antithrombotic component maybe included in the chemical composition of a polymeric filament. Inother embodiments, a flexible cord may be coated with a polymer thatreleases an anticoagulant and thereby reduces the risk of thrombusformation. In other embodiments, additional therapeutic agents orcombinations of agents may be used, e.g., antibiotics andanti-inflammatory agents. In some embodiments, the flexible cord can bemaneuvered through a catheter.

The cross-sectional configuration of the flexible cord can be anysuitable shape, such as round, oval, rectangular, square, etc. In someembodiments, the flexible cord may have a flattened cross-sectionalshape, such as a “ribbon” shape. In other embodiments, the flexible cordmay be a combination of shapes, such as for example, a flexible cordwhich is round on two sides with a flat surface on the opposing twosides. In some embodiments the entire flexible cord has the same shape,and in other embodiments, at least a portion of the flexible cord mayhave a different shape, e.g., a ribbon configuration, or at least aportion of the cord which is flattened, or has a flat surface. In someembodiments, the greatest outer diameter of the flexible cord may rangefrom 0.1 mm to 0.6 mm, such as from 0.149 mm to 0.4 mm, or 0.15 mm to0.2 mm. In some embodiments, the entire flexible cord has the samediameter. In other embodiments, at least a portion of the cord has adifferent diameter, e.g., a smaller diameter. In some embodiments, atleast a portion of the cord may have both a different configuration anda different diameter, e.g., a portion of the cord may have a flatsurface, where the portion of the cord having a flat surface has alargest outer diameter larger than the remainder of the cord. In someembodiments, the flexible cord does not comprise a knot.

A portion of the flexible cord between the first end and second ends isconfigured to be secured to tissue, such as cardiac tissue located belowa cardiac valve leaflet. In some embodiments, a portion of the flexiblecord between the first end and second ends can be secured to aprosthesis, or other device that substitutes for or supplements amissing or defective part of the body. The portion of the flexible cordbetween the first end and the second end that is configured to besecured to tissue can have the same shape and diameter as the remainderof the flexible cord, or in some embodiments it may have a differentshape or diameter as the remainder of the flexible cord, as in theembodiments discussed above. For example, the portion of the cordbetween the first end and the second end that is configured to beattached to a second tissue may be flattened, or have a smaller orlarger diameter.

The portion of the flexible cord between the first end and the secondend that is configured to be secured to tissue can further include areinforcing member. A reinforcing member is an element which dispersesthe force of the securing flexible cord over a larger surface area. Insome embodiments, the reinforcing member can be a pledget. Pledgets aregenerally buttressing or cushioning pads through which a suture or cordcan be threaded, in order to prevent the suture strand or flexible cordfrom cutting into the tissue. A reinforcing member can be made of anysuitable biologically compatible, needle pierceable resilient materialsufficiently soft and flexible to effectively prevent damage to thetissue, e.g., papillary muscle. A reinforcing member is further made ofmaterial strong enough to resist pull-through by the flexible cord orsuture to which it is mounted. The reinforcing member includes a topsurface and a bottom surface, and can be configured in a variety ofsizes and shapes, including rectangular, circular, elliptical, etc. Forexample, in certain embodiments the length of the reinforcing member mayrange from 1 mm to 10 mm, such as from 2 mm to 8 mm, or 3 mm to 4 mm.The width of the reinforcing member in some cases may range from 1 mm to10 mm, such as from 2 mm to 8 mm, or 3 mm to 4 mm. In some embodiments,the thickness of the reinforcing member may range from 0.1 mm to 2 mm,such as from 0.2 mm to 0.5 mm, or 0.3 mm to 0.4 mm. The reinforcingelements may be fabricated of fabric, or felt, includingpolytetrafluoroethylene and polyester felt,polytetrafluoroethylene(PTFE), expanded PTFE, polyester and the like. Insome embodiments, an antithrombotic component may be included in thechemical composition of the reinforcing member. In other embodiments, areinforcing member may be coated with a polymer that releases ananticoagulant and thereby reduces the risk of thrombus formation. Inother embodiments, additional therapeutic agents or combinations ofagents may be used, e.g., antibiotics and anti-inflammatory agents.

In addition, the reinforcing element can have at least one openingwherein the flexible cord element may pass through. In otherembodiments, the flexible cord is attached to the reinforcing elementwithout passing through an opening, e.g., the flexible cord has beenpulled through with a needle. In some embodiments, the reinforcingelement is mounted such that it is substantially fixed in a position onthe flexible cord. For example, the reinforcing element can be sewn, orglued, or fused in any suitable manner so that it is fixed in positionon the flexible cord, e.g., fixed in position halfway between the firstand second ends of the flexible cord, such that the reinforcing elementdivides the flexible cord into two segments of equal length. In otherembodiments, the reinforcing element is mounted such that it is slidablymounted on a flexible cord. By “slidably” is meant that the reinforcingelement is attached to the flexible cord so that it is secure yet it ispossible to move the reinforcing element along at least part of thelength of the cord. For example, a flexible cord can have a reinforcingelement (e.g., a pledget) initially positioned halfway between the firstand second ends of the flexible cord. In using the synthetic chorddevice, it may be desirable to move the reinforcing element to aposition closer to the first end before securing the reinforcing elementto a tissue.

The synthetic chord devices further include attachment elements on boththe first end and the second end of a flexible cord. The attachmentelements are configured to attach a flexible cord, such as thosedescribed above, to a tissue, e.g., a cardiac valve leaflet. Anattachment element is an element which includes a tissue piercing memberand a securing member. The attachment element may be configured suchthat one or both of the tissue piercing members is attached to thesecuring member with a flexible member such as a suture. The attachmentelement may also be configured such that the tissue piercing member isdirectly attached to the securing member. One or both of the tissuepiercing members may in some embodiments be releaseably coupled to asecuring member. In other embodiments, the attachment element may beconfigured such that one or both of the tissue piercing members isattached to a flexible member, such as a suture, which in turn isreleaseably coupled to the securing member. The coupling between theflexible member (and, thus, the tissue piercing member) and the securingmember may be configured to actuate closure of the securing member uponrelease of the flexible member (or piercing member), as discussed below.For example, the coupling may hold a compression spring (which ispositioned around a securing member) in a compressed state to brace thesecuring member open and releaseably lock or secure the securing memberto the flexible member (or piercing member). In some embodiments, theattachment element can be secured to a prosthesis, or other device thatsubstitutes for or supplements a missing or defective part of the body.

A flexible member as discussed above, such as a suture or a wire, can beformed from any suitable biocompatible material such as cotton, nylon,polyester, polypropylene, polyglycolic acid, polylactide, lactic acid,trimethlylene carbonate, polycaprolactone, or polydiaxanone orcopolymers or homopolymers thereof, or a metal alloy, such as nitinol orstainless steel, a polymeric material, or any other suitable materialand equivalents thereof. The material may be non-stretchable orstretchable, and have various cross-sectional diameters. In someembodiments, the flexible member does not comprise a knot. The flexiblemembers may have a cross-sectional diameter of 0.003 inch, for example.The diameter and length of the flexible member will vary depending onthe specific application. The flexible members, e.g., sutures, may beattached to the piercing members by crimping or swaging or otherwiseattaching the piercing member or needle onto the flexible member, gluingthe flexible member to the piercing member or needle, or any othersuitable attachment method. Flexible members can also have variouscross-sectional shapes, such as round, oval, etc.

A piercing member, or penetrating member is any device that can be usedin a surgical, endovascular, or other interventional procedure that canbe used to pierce through tissue, e.g., a needle. In some embodiments,the piercing member can also be used to pierce a prosthesis, e.g.,synthetic valve. Piercing members that can be used in the subjectdevices include, but are not limited to, a conventional surgical needle,etc. The surgical needles useful in the devices of the present inventioninclude conventional cardiac surgical needles and equivalents thereof.Suitable surgical needles can be manufactured from stainless steel, astainless steel alloy, or any other suitable material, such as apolymeric material. The material can also have special coatings andsharpening methods that facilitate atraumatic tissue penetration. Theshapes and sizes of the surgical needles can vary with the type anddesign of the needle. In some embodiments, the surgical needles have acurved or arced shape. In some embodiments, the needles may bepermanently “swaged” or attached to the suture material. In someembodiments, the suture may be designed to come off the suture with asharp straight tug (e.g., “pop-offs”).

Suitable lengths for the piercing members that are in the form of aneedle can range in some embodiments from 4 mm to 70 mm, such as from 9mm to 65 mm, or 20 mm to 40 mm. The diameter of the piercing member mayrange in certain embodiments from 0.05 mm to 0.6 mm, such as from 0.07mm to 0.5 mm, or 0.1 mm to 0.4 mm. In some embodiments, the diameter ofat least a portion of a piercing member is greater than the diameter ofan attached flexible member or attached securing member, coupled so thatthe attached flexible member or attached securing member can easily bepulled through an opening formed in a tissue (or other material) by thepiercing member, e.g., needle. The distal end or tip of the piercingmember can be rigid to facilitate penetration of tissue. The remaininglength of the piercing member can be rigid or flexible to facilitatemovement of the piercing member through the tissue or other material.The tips can have various configurations and can, for example, have apiercing point, tapered point, or have a cutting or reverse cuttingconfiguration for example, and have a shape such as conical, tapered, orgrounded to attain a three or four facet tip. Piercing members can haveany suitable shape or radius of curvature. Piercing members can have anysuitable cross-sectional shape which may vary in different sections ofthe needle, e.g., round, rectangular, etc. In some embodiments, thepiercing member can also be integrally formed with the flexible member(e.g., both piercing member and flexible member formed of the samematerial).

The attachment elements of the subject devices also include a securingmember. A securing member is any device that can be used in a surgical,endovascular, or other interventional procedure that can be used tosecure a flexible cord, or suture, e.g., an artificial mitral valvechorda tendinea. Suitable material for securing members can includeshape memory materials, which are materials that have a temperatureinduced phase change, e.g., a material that if deformed when cool,returns to its “undeformed”, or original, shape when warmed. Suitablematerial includes but is not limited to metals such as a nickel-titanium(NiTi) alloy (e.g., nitinol), a nickel-cobalt alloy, another cobaltalloy, alloys of CuZnAl, a thermoset plastic, stainless steel, asuitable biocompatible shape-memory material, a suitable biocompatiblesuperelastic material, combinations thereof, and any suitablebiocompatible shape memory alloy that can return to its undeformed, ororiginal shape when warmed to body temperature, e.g., human bodytemperature. A securing member can have any suitable configuration. Insome embodiments, for example, a securing member can have an anchorconfiguration, such that the arm segments of the anchoring members areconstructed of a biocompatible material capable of being preset into ananchor shape. In another embodiment, a securing member can have a loopshape, such that the securing member is constructed of a biocompatiblematerial capable of being preset into a loop shape. In some embodiments,a securing member can have an umbrella configuration, such that the armsegments of the anchoring members are constructed of a biocompatiblematerial capable of being preset into an umbrella shape. The securingmember may in other embodiments have various undeformed or deformedconfigurations such as a “parachute” configuration, an ellipse, atriangle, a square, a rectangle, spiral, conical, or other geometricshape, etc.

As discussed above, in some embodiments, the securing member may bereleaseably coupled to a tissue piercing member. In some embodiments, aflexible member, such as a suture, may be provided between at least oneof the tissue piercing members and the securing member to facilitatethreading the securing member.

In some embodiments, the securing member may secure the flexible cordwithout piercing the adjacent tissue, e.g., in the same manner as asurgical knot prevents a suture from pulling back through a tissue. Inother embodiments, the securing member may secure the flexible cord byat least partially piercing the adjacent tissue. In some embodiments,the securing member may do both.

In some embodiments, the securing member is a self-closing fastener,which is any device that can be used in a surgical, endovascular, orother interventional procedure that can secure a flexible cord to tissueor other material (e.g., secure a flexible cord to a cardiac valveleaflet). In some embodiments, the self-closing fasteners can be made ofa shape memory material is meant a material that exhibits the shapememory effect, as discussed above. The shape memory alloy is preferablyselected with a transformation temperature suitable for use with astopped heart condition where cold cardioplegia has been injected fortemporary paralysis of the heart tissue (e.g., temperatures as low as8-10 degrees Celsius). The shape memory alloy may also be heatactivated, or a combination of heat activation and pseudoelasticproperties may be used. Self-closing fasteners that can be used in thesubject devices include, but are not limited to, nitinol clips, such asthe V60 U-clip device™ (Medtronic Inc.) or any other preconfiguredattachment device, etc.

A self-closing fastener can be held in an “open” configuration by adelivery mechanism that holds and retains the fastener in an openconfiguration. In some embodiments, a locking element can be included toconnect the ends of the securing member when the securing member is inits closed position to prevent possible opening of the securing memberover time. The locking element can in some embodiments be integrallyformed with the securing member. In some embodiments, the self-closingfastener can include a release mechanism. Further details ofself-closing fasteners that can be adapted for use with the presentdevices can be found in U.S. Pat. Nos. 6,913,607, 6,641,593, 6,613,059,6,607,541, and 6,514,265.

As discussed above, a self-closing fastener can have any suitableconfiguration, including but not limited to an anchor configuration, aloop configuration, an “umbrella” or “parachute” configuration, anellipse, a triangle, a square, a rectangle, spiral, conical, or othergeometric shape, etc.

FIGS. 1A and B provide a view of the device in accordance with anembodiment of the invention. In FIG. 1A, the synthetic chord device ofthe subject invention is shown in an un-deployed state. The piercingmember (e.g., a needle) is shown as element 110. The un-deployedself-closing fastener 130 is attached to the needle by flexible member(e.g., suture) 120. Flexible cord 140 is shown with a reinforcing member150 (e.g., a pledget).

In FIG. 1B, the synthetic chord device of the subject invention is shownin a deployed state. The needle has been removed, and the self-closingfastener has been deployed, shown as element 135.

FIGS. 5A and B provide a view of the device in accordance with anotherembodiment of the invention, in which the self-closing fastener has an“umbrella” configuration. In FIG. 5A, the synthetic chord device of thesubject invention is shown in an un-deployed state. The un-deployedself-closing fastener 530 is attached to a needle by flexible member(not shown). Flexible cord 540 is shown with reinforcing member 550.

In FIG. 5B, the synthetic chord device of the subject invention is shownin a deployed state. The self-closing fastener has been deployed, shownas element 535.

Methods

The subject devices find use in methods for fastening a tissue, such asa cardiac valve leaflet, to a second tissue, such as a papillary muscle,with a flexible cord (e.g., a synthetic mitral valve chorda tendinea).The subject devices therefore find use in methods in which a prolapsedcardiac valve leaflet, such as a mitral valve leaflet, is repaired. Thesubject devices can be used in an open surgical procedure, a minimallyinvasive surgical procedure, an endovascular procedure, or otherinterventional procedure.

Methods for repair of a cardiac valve, such as a mitral valve, arediscussed below. When performing a conventional heart valve repairprocedure, the surgeon makes incisions into the thoracic cavity andpericardium, and then into aorta or myocardium in order to have accessto the damaged heart valve. The procedure may be an open procedure inwhich the sternum is opened and the ribs are spread with a conventionalretractor, or a minimally invasive procedure wherein the heart and heartvalve are accessed through minimally invasive openings in the thoraciccavity, such as through trocar cannulas or small incisions in theintercostal spaces. The heart may also be accessed through the lumen ofan artery. The minimally invasive procedures can be viewed remotelyusing a camera and monitor, or in some cases directly.

FIG. 2 depicts a schematic drawing of the left side of the heart. Theaortic arch 210, left atrium 215, and left ventricle 220 are shown, withthe mitral valve 250 located between the left ventricle and the leftatrium. The chordae tendineae are shown as elements 240, attached to theleaflets of the mitral valve on one end, and the papillary muscle 230 inthe left ventricle on the other end.

After exposure of the mitral valve and the subvalvular area, the desiredlength of the neochord, or flexible cord, is determined by measuring thedistance between the prolapsed leaflet and the cardiac tissue locatedbelow the prolapsed mitral valve leaflet using methods that are wellknown in the art. The desired length for the flexible cord can bedetermined using any suitable measuring device, such as a caliper, or aMohr Suture Ruler Device™ (Geister, Tuttlingen, Germany). For example, acaliper or sterile disposable flexible tape measure can be used toassess the correct length for the synthetic mitral valve chordae bymeasuring the distance between the tip of the papillary muscle and theedge of a non-prolapsing segment of the mitral valve leaflet. Themeasurement can also be confirmed by comparison with pre-operativetransesophageal echocardiography (TEE).

An illustration of a rupture, or breakage of one of the chorda tendineawhich can be repaired using the methods and devices of the subjectinvention is shown in FIG. 3. The ruptured, or broken chorda tendinea isshown as element 350. The leaflets of the mitral valve now no longercoapt, or close, and during systole, blood can flow from the leftventricle back into the left atrium, i.e., mitral regurgitation.

The synthetic chord device having a flexible cord with the desiredlength, or the closest to the desired length, is then selected fromamong a set of synthetic chord devices. The set of synthetic chorddevices can include two or more flexible cords of the same or ofdifferent lengths, such as three cords, or four cords, etc.

The piercing member on the first end, e.g., a needle, is first advancedthrough the cardiac tissue below the prolapsed mitral valve leaflet,e.g., a papillary muscle, and pulled through until the reinforcingelement, e.g., a pledget, is in substantial contact with a surface ofthe papillary muscle. The needle is then advanced through the leaflet ofthe prolapsed mitral valve until the securing member, e.g., aself-closing fastener such as a nitinol clip, has passed through theleaflet.

The position of the prolapsed valve leaflet may be adjusted bycoordinating the tension of the cord and the location of the leaflet.For example, a practitioner (e.g., a doctor, surgeon, technician, etc.)may move the prolapsed valve into a correct (e.g., non-prolapsed)position by adjusting the position of the valve leaflet directly bypushing against the anchor attached to the valve leaflet (e.g., usingthe fastener to push against the anchor and applying tension to thecord). The valve leaflet position may be adjusted in real-time in abeating heart (e.g., using echocardiography). For example, the valveleaflet may be repositioned while monitoring mitral regurgitation (MR).Once any MR is reduced or eliminated, the valve leaflet is in thecorrect position.

Once the valve leaflet is positioned correctly, the attachment membercan then be deployed (e.g., the self-closing fastener deploys, orcloses, for example, as shown in FIGS. 1B and 5B). The piercing memberon the second end, e.g., a needle, is then advanced through thepapillary muscle below the prolapsed mitral valve leaflet, therebysecuring the pledget against the papillary muscle. The second tissuepiercing member, e.g., needle, is then advanced through the sameprolapsed mitral valve leaflet, until the second securing member haspassed through the leaflet. The second attachment element is thendeployed, as discussed above. It should be noted that the number ofsynthetic chord devices required to secure the connecting tissuestogether may vary depending on the procedure and the anatomy.

FIG. 4A shows an embodiment of a repair of the ruptured chorda tendineawith a synthetic chord device 470 of the subject invention. The flexiblecord 460 is attached to the mitral valve leaflet at both ends withsecuring members 490, which in this embodiment have a ring shape.Flexible cord 460 is shown secured to the tissue below the mitral valveleaflet (e.g., the papillary muscle) with reinforcing member 480. Afterrepair, the leaflets of the mitral valve 250 now coapt, or close, andblood can no longer flow from the left ventricle back into the leftatrium during systole.

FIG. 4B shows another embodiment of a repair of the ruptured chordatendinea with a synthetic chord device 470 of the subject invention. Theflexible cord 460 is attached to the mitral valve leaflet at both endswith securing members 495, which in this embodiment have a four-pronged“umbrella” shape, similar to the embodiment shown in FIGS. 5A and B. Inthis embodiment, the surface area of the mitral valve leaflet which iscontacted by the securing member is increased. Flexible cord 460 isagain shown secured to the tissue below the mitral valve leaflet (e.g.,the papillary muscle) with reinforcing member 480.

FIG. 6 shows an embodiment of a repair of ruptured chordae tendineae ofboth the mitral and tricuspid valves with synthetic chord devices of thesubject invention. In this view, the left atrium is shown as element605, the left ventricle is element 610; the right atrium is element 615,and the right ventricle is shown as element 620. The flexible cords 660are attached to the mitral valve 650 or tricuspid valve 655 leaflet atboth ends with securing members 690. Flexible cord 660 is shown securedto the tissue below the valve leaflets (e.g., papillary muscle, 630)with reinforcing members 680. After repair, the leaflets of the mitralvalve 650 and tricuspid valve 655 now coapt, or close, and blood can nolonger flow from the ventricles back into the atria during systole.

By this method, a prolapsed mitral valve leaflet can be repaired bysecuring the leaflet to the papillary muscle below. Using the methodsand devices of the subject invention, a mitral valve repair procedurecan be successfully completed without the need for the time-consumingstep of cutting the desired length of synthetic cord while the patientis on the operating table, thereby decreasing the amount of time neededto place a patient on cardio-pulmonary bypass. In addition, the subjectmethods and devices obviate the need for tying sutures and ensuring thatthe suture material does not become tangled, difficulties which areexacerbated by the small size of the tissues involved and the oftenlimited field of the operation.

Any appropriate prolapsed valve leaflet may be treated as describedherein, including mitral valve leaflets and tricuspid valve leaflets.Further, these methods may be performed using one or more catheters orusing non-catheter surgical methods, or using a combination ofcatheter-type surgical methods and non-catheter type surgical methods.The methods of the subject invention may also be used in combinationwith other surgical procedures, e.g. replacement of a mitral valveannulus, etc.

In some variations, the flexible cord may be advanced via one or morecatheters to the proximity of the prolapsed valve leaflet in ananterograde approach (e.g., from above the mitral valve). Alternatively,the flexible cord may be advanced via a retrograde approach (e.g., frombelow the mitral valve). In all of the methods described herein, thecardiac tissue located below the prolapsed valve (to which one of theanchors is secured) may be selected from the group consisting of apapillary muscle and a ventricular wall.

The subject methods also include the step of diagnosing a patient inneed of cardiac valve repair, e.g., mitral valve repair. Primary mitralregurgitation is due to any disease process that affects the mitralvalve device itself. The causes of primary mitral regurgitation includemyxomatous degeneration of the mitral valve, infective endocarditis,collagen vascular diseases (ie: SLE, Marfan's syndrome), rheumatic heartdisease, ischemic heart disease/coronary artery disease, trauma. balloonvalvulotomy of the mitral valve, certain drugs (e.g. fenfluramine). Ifvalve leaflets are prevented from fully coapting (i.e., closing) whenthe valve is closed, the valve leaflets will prolapse into the leftatrium, which allows blood to flow from the left ventricle back into theleft atrium, thereby causing mitral regurgitation.

The signs and symptoms associated with mitral regurgitation can includesymptoms of decompensated congestive heart failure (ie: shortness ofbreath, pulmonary edema, orthopnea, paroxysmal nocturnal dyspnea), aswell as symptoms of low cardiac output (i.e., decreased exercisetolerance). Cardiovascular collapse with shock (cardiogenic shock) maybe seen in individuals with acute mitral regurgitation due to papillarymuscle rupture or rupture of a chorda tendinea. Individuals with chroniccompensated mitral regurgitation may be asymptomatic, with a normalexercise tolerance and no evidence of heart failure. These individualshowever may be sensitive to small shifts in their intravascular volumestatus, and are prone to develop volume overload (congestive heartfailure).

Findings on clinical examination depend of the severity and duration ofmitral regurgitation. The mitral component of the first heart sound isusually soft and is followed by a pansystolic murmur which is highpitched and may radiate to the axilla. Patients may also have a thirdheart sound. Patients with mitral valve prolapse often have amid-to-late systolic click and a late systolic murmur.

Diagnostic tests include an electrocardiogram (EKG), which may showevidence of left atrial enlargement and left ventricular hypertrophy.Atrial fibrillation may also be noted on the EKG in individuals withchronic mitral regurgitation. The quantification of mitral regurgitationusually employs imaging studies such as echocardiography or magneticresonance angiography of the heart. The chest x-ray in patients withchronic mitral regurgitation is characterized by enlargement of the leftatrium and the left ventricle. The pulmonary vascular markings aretypically normal, since pulmonary venous pressures are usually notsignificantly elevated. An echocardiogram, or ultrasound, is commonlyused to confirm the diagnosis of mitral regurgitation. Color dopplerflow on the transthoracic echocardiogram (TTE) will reveal a jet ofblood flowing from the left ventricle into the left atrium duringventricular systole. Because of the difficulty in getting accurateimages of the left atrium and the pulmonary veins on the transthoracicechocardiogram, a transesophageal echocardiogram (TEE) may be necessaryto determine the severity of the mitral regurgitation in some cases. Theseverity of mitral regurgitation can be quantified by the percentage ofthe left ventricular stroke volume that regurgitates into the leftatrium (the regurgitant fraction). Other methods that can be used toassess the regurgitant fraction in mitral regurgitation include cardiaccatheterization, fast CT scan, and cardiac MRI.

Indications for surgery for chronic mitral regurgitation include signsof left ventricular dysfunction. These include an ejection fraction ofless than 60 percent and a left ventricular end systolic dimension(LVESD) of greater than 45 mm.

The description of the present invention is provided herein in certaininstances with reference to a subject or patient. As used herein, theterms “subject” and “patient” refer to a living entity such as ananimal. In certain embodiments, the animals are “mammals” or“mammalian,” where these terms are used broadly to describe organismswhich are within the class mammalia, including the orders carnivore(e.g., dogs and cats), rodentia (e.g., mice, guinea pigs, and rats),lagomorpha (e.g., rabbits) and primates (e.g., humans, chimpanzees, andmonkeys). In certain embodiments, the subjects, e.g., patients, arehumans.

Kits

Also provided are kits that at least include the subject devices. Thesubject kits at least include a synthetic chord device of the subjectinvention and instructions for how to use the synthetic chord device ina procedure.

In some embodiments, the kits can include a set of two or more syntheticchord devices. In other embodiments, a set of synthetic chord devicescan include at least three synthetic chord devices, e.g., four or more,five or more, six or more, etc.

In some embodiments, a set of synthetic chord devices includes two ormore synthetic chord devices in which at least two of the syntheticchord devices have flexible cords of different lengths. In otherembodiments, the flexible cord portions of the synthetic chord devicesare all of differing lengths. In some embodiments, a set of syntheticchord devices can have two or more synthetic chord devices in which theflexible cords are of the same length. A set of synthetic chord devicescan therefore have two or more some synthetic chord devices in whichsome are of the same length, and some are of a different length. Forexample, in one embodiment a set of six synthetic chord devices can havetwo synthetic chord devices in which the flexible cord portion is 16 mmin length, which can provide two segments with a length of 8 mm; twosynthetic chord devices in which the flexible cord portion is 20 mm inlength, which can provide two segments with a length of 10 mm; and twosynthetic chord devices in which the flexible cord portion is 24 mm inlength, which can provide two segments with a length of 12 mm. Inanother embodiment, a set of synthetic chord devices can have foursynthetic chord devices in which the flexible cord portion in all ofthem is 20 mm in length, such that each flexible cord portion canprovide two segments with a length of 10 mm.

In addition, in some embodiments, the synthetic chord devices can becolor-coded, such that a desired length of the synthetic mitral valvechord, or flexible cord element, can be easily determined. For example,a package with multiple synthetic chord devices can have sutures of twodifferent colors arranged in an alternating pattern to allow a medicalpractitioner (e.g., scrub nurse) to readily distinguish one syntheticchord device from another. For example, a set of ten synthetic chorddevices in a kit can be arranged in two horizontal rows of five in eachrow. An exemplary arrangement of associated suture colors would be, inthe top row: white, green, white, green, white, and in the bottom row:green, white, green, white, green. (further details of packaging thatcan be adapted for use with the synthetic chord devices of the subjectinvention are disclosed in U.S. Pat. No. 6,029,806, incorporated hereinby reference). In this manner, a scrub nurse can readily associate eachpair of tissue-piercing members (e.g., needles) with the synthetic chorddevice containing the correct length of synthetic mitral valve chord, orflexible cord. By color coding the synthetic chord devices withalternating, contrasting suture colors, more synthetic chord devices canbe stored in a package of a given size without causing confusion. Thetwo needles associated with each synthetic chord device can besufficiently separated to allow grasping of each needle with a needleholder, while maintaining identification of the pair of needles asbelonging to the same synthetic chord device. The kit can also include ameasuring tool, which can be disposable, for determining a desiredlength of a synthetic chord by measuring a desired distance, such as thedistance between a prolapsed cardiac valve leaflet and cardiac tissuelocated below the prolapsed cardiac valve leaflet., including but notlimited to any suitable measuring device, such as a caliper, a MohrSuture Ruler Device™ (Geister, Tuttlingen, Germany), or steriledisposable flexible tape measure.

The instructions for using the devices as discussed above are generallyrecorded on a suitable recording medium. For example, the instructionsmay be printed on a substrate, such as paper or plastic, etc. As such,the instructions may be present in the kits as a package insert, in thelabeling of the container of the kit or components thereof (i.e.associated with the packaging or subpackaging) etc. In otherembodiments, the instructions are present as an electronic storage datafile present on a suitable computer readable storage medium, e.g.,CD-ROM, diskette, etc. The instructions may take any form, includingcomplete instructions for how to use the device or as a website addresswith which instructions posted on the world wide web may be accessed.

The following example is offered by way of illustration and not by wayof limitation.

EXPERIMENTAL

A patient is prepared for a mitral valve prolapse repair procedure in aconventional manner. The patient is anesthetized using conventionalanesthesia and anesthesiology procedures.

The patient undergoes an intraoperative transesophageal echocardiographyto determine the mechanism of the mitral regurgitation (MR), and toestimate the required length for the synthetic mitral valve neochordae.The intraoperative transesophageal echocardiography also serves as abaseline evaluation for assessing the quality of the repair, and forfollow-up evaluation.

The patient's skin overlying the sternum and surrounding areas isswabbed with a conventional disinfecting solution. Next, the surgeonaccesses the patient's thoracic cavity via a right anterolateralmini-thoracotomy, through a 3 cm incision. Three additional small 10 mmports are made for video camera, a left atrial retractor, and atransthoracic aortic clamp.

The heart is then accessed by opening the pericardium. Next, the patientis placed on cardiopulmonary bypass in a conventional manner and thepatient's heart is stopped from beating in a conventional manner. Thesurgeon then performs the mitral valve repair in the following manner:The valve is accessed through an incision in the left atrium or acrossthe atrial septum if bi-caval cannulation is utilized forcardiopulmonary bypass. After exposure of the mitral valve and thesubvalvular area, the desired length of the neochord, or flexible cord,is determined by measuring the distance between the tip of the papillarymuscle and the edge of a non-prolapsing segment of the mitral valveleaflet.

A synthetic chord device as depicted in FIG. 1 is selected from a set ofsynthetic chord devices of the present invention based on themeasurement. The needle on the first end is advanced through thepapillary muscle located below the mitral valve leaflet, and pulledthrough until the pledget is in substantial contact with a surface ofthe papillary muscle. The needle is then advanced through the leaflet ofthe prolapsed mitral valve until the un-deployed Nitinol U-clip haspassed through the leaflet.

Once the length of the synthetic mitral valve chord and the function ofthe mitral valve has been assessed, the Nitinol U-clip is deployed. Theneedle on the second end is advanced through the papillary muscle belowthe prolapsed mitral valve leaflet, adjacent to the site of the firstend of the flexible cord, thereby securing the pledget against thepapillary muscle. The second needle with the un-deployed Nitinol U-clipis then advanced through the same prolapsed mitral valve leaflet untilthe Nitinol U-clip has been pulled through the leaflet.

Once the length of the synthetic mitral valve chord and the function ofthe mitral valve has been assessed, the second Nitinol U-clip isdeployed.

Post-repair valve competency can be assessed by filling and pressurizingthe left ventricle with saline and observing the valve. The incisionsare then closed and the patient weaned, or removed, from cardiopulmonarybypass. After weaning the patient from cardiopulmonary bypass, valvefunction is examined with transesophageal echocardiography or likemeans. The chest and skin incisions are then closed to complete theprocedure.

All publications and patent applications cited in this specification areherein incorporated by reference as if each individual publication orpatent application were specifically and individually indicated to beincorporated by reference. The citation of any publication is for itsdisclosure prior to the filing date and should not be construed as anadmission that the present invention is not entitled to antedate suchpublication by virtue of prior invention.

Although the foregoing invention has been described in some detail byway of illustration and example for purposes of clarity ofunderstanding, it is readily apparent to those of ordinary skill in theart in light of the teachings of this invention that certain changes andmodifications may be made thereto without departing from the spirit orscope of the appended claims.

1. A synthetic chord device comprising: (a) a flexible cord having afirst end and a second end; (b) a first attachment element at said firstend of said cord configured to attach said cord to a first location at afirst tissue; (c) a second attachment element at a second end of saidcord configured to attach said cord to a second location at said firsttissue; wherein said first and second attachment elements each comprisea piercing member and a securing member and at least a portion of saidcord between said first end and said second end is configured to besecured to a second tissue.
 2. The synthetic chord device according toclaim 1, wherein said flexible cord has a length ranging from 16 mm to48 mm.
 3. The synthetic chord device according to claim 1, wherein saidsecuring member of each of said first and second attachment elements isa self-closing fastener.
 4. The synthetic chord device according toclaim 3, wherein said securing member of each of said first and secondattachment elements comprises a shape memory material.
 5. The syntheticchord device according to claim 4, wherein said shape memory materialcomprises a nickel titanium alloy.
 6. The synthetic chord deviceaccording to claim 1, wherein said cord comprises a polymer.
 7. Thesynthetic chord device according to claim 6, wherein said cord comprisespolytetrafluoroethylene (PFTE).
 8. The synthetic chord device accordingto claim 1, wherein said tissue is cardiac tissue, selected from thegroup consisting of a papillary muscle and a ventricular wall.
 9. Thesynthetic chord device according to claim 1, wherein said portion ofsaid cord configured to be secured to said tissue comprises areinforcing element.
 10. The synthetic chord device according to claim9, wherein said reinforcing element is a pledget.
 11. The syntheticchord device according to claim 1, wherein said piercing member of eachof said first and second attachment elements comprises a needle.
 12. Amethod for connecting tissue comprising: (a) securing a flexible cordhaving a first end and a second end to a first tissue; (b) attachingsaid first end to a second tissue with a first attachment element; (c)attaching said second end to said second tissue with a second attachmentelement; wherein said first and second attachment elements each comprisea piercing member and a securing member and said attaching of said firstand second ends comprises removing said piercing element from each ofsaid first and second attachment elements.
 13. The method according toclaim 12, further comprising: (a) determining a desired length of saidflexible cord by measuring a desired distance between said first tissueand said second tissue; and (b) selecting a synthetic chord devicehaving a flexible cord with said desired length from a set of two ormore synthetic chord devices.
 14. The method according to claim 12,wherein said flexible cord has a length ranging from 16 mm to 48 mm. 15.The method according to claim 12, wherein said securing member is aself-closing fastener.
 16. The method according to claim 15, whereinsaid self-closing fastener comprises a shape memory material.
 17. Themethod according to claim 16, wherein said shape memory materialcomprises a nickel titanium alloy.
 18. The method according to claim 12,wherein said cord comprises a polymer.
 19. The method according to claim18, wherein said flexible cord comprises polytetrafluoroethylene (PFTE).20. The method according to claim 12, wherein the portion of said cordconfigured be secured to said first tissue comprises a reinforcingelement.
 21. The method according to claim 21, wherein said reinforcingelement is a pledget.
 22. The method according to claim 12, wherein saidpiercing member is a needle.
 23. A method for treating a prolapsedcardiac valve leaflet, said method comprising: (a) securing a flexiblecord having a first end and a second end to cardiac tissue located belowa cardiac valve leaflet; (b) attaching said first end to said cardiacvalve leaflet with a first attachment element; (c) attaching said secondend to said cardiac valve leaflet with a second attachment element;wherein said first and second attachment elements each comprise apiercing member and a securing member and said attaching of said firstand second ends comprises removing said piercing element from each ofsaid first and second attachment elements.
 24. The method according toclaim 23, further comprising: (a) determining a desired length of saidflexible cord by measuring a distance between a prolapsed cardiac valveleaflet and cardiac tissue located below said prolapsed cardiac valveleaflet; and (b) selecting a synthetic chord device having a flexiblecord with said desired length from a set of two or more synthetic chorddevices. 25-42. (canceled)